Andrzej Chimiak

Synthesis of sweet DOPA peptide and its analogues.

SummaryAsp-DOPA-OMe, Asp-DOPA-OnBu, and Asp-dopamine were prepared according to the new general procedure described for DOPA dipeptides.

N-Hydroxyamino Acids and Their Derivatives

N-Hydroxyamino acids should, at present, be treated as a new, separate, characteristic group of amino acids. This is necessitated by the particular biological action of these compounds and their derivatives. Although α-N-hydroxyamino acids were first discovered by Miller and Plochl (1) as early as 1893, they have aroused particular interest mainly in the last twenty years.

Oxidation of amino acid. Part V. A novel synthesis of N6-Acetyl-N6-hydroxylysine from lysine

Abstract N 6 -Acetyl-N 6 -L-hydroxylysine was synthesized from L-lysine by oxidation of the amino group in the N 2 -benzyloxycarbonyl-L-lysine tert- butyl ester with benzoyl peroxide and subsequent acetylation.

Catechoyl-dipeptides as leucine aminopeptidase inhibitors

Several 2,3- (and 3,4)-dihydroxybenzoyl-dipeptides (5) have been obtained as new ligands able to interact with therapeutically important metalloproteases. Some of them appeared to be strong inhibitors of leucine aminopeptidase [EC 3.4.11.1].

Removal of239Pu from mice with 3,4,3 LICAM(C) or N, N′, N″, N‴-tetra-(2,3-dihydroxybenzoyl)-spermine

SummaryMale mice SAS/4 were injected i.v. with239Pu citr(IV) 0.27 µCi⋅kg−1−9.99 kBq⋅kg−1. After 1 h 30 µmol ⋅ kg−1 of 3,4,3 LICAM(C), N, N′, N″, N‴-tetra-(2,3-dihydroxybenzoyl)-spermine or Na3CaDTPA as a reference compound was given intraperitoneally. After 4 days the animals were sacrified and the Pu content in livers, kidneys, femurs and carcasses was determined by the liquid scintillation method. It was found that, as compared with the control, 3,4,3 LICAM(C) removed 83% of the Pu activity deposited in the liver, 71% of that in the femur and 79% of the Pu in the whole body. The Pu content in the kidneys exceeded the control value by about 50%. Na3CaDTPA removed 96, 86, 40 and 72% of plutonium from the liver, kidneys, femurs and carcasses respectively.Tetra-DHB-spermine caused the excretion of 50, 57 and 39% of Pu from liver, bone and whole body respectively. The retention of Pu in the kidneys was increased to 400% of the control value.

Synthesis of Amino Acids Analogues of Citric Acid Siderophores

2-tert-buiyl- Three amino acid analogues of citric acid siderophores were synthesized. The synthetic strategy involved condensation of 2-tert-butyl-1,3-di(N-hydroxysuccinimidyl) or 1,3-bis(pentachlorophenyl)citrates with N-ethyl-ω-aminoalkylhydroxamates. The examination of biological properties of the obtained compounds revealed their poor, if any siderophore activity and thus confirmed the structural requirements previously suggested for siderophores of this type.

Efficacy and toxicity of N,N',N″,N'″-tetra(2,3,4-trihydroxybenzoyl)-spermine for decorporation of 239Pu from mice

Male SAS/4 mice were injected i.v. with 6.6 kBq 239Pu-citrate. After 1 or 24 h a single i.p. injection of 15 or 30 mumol kg-1 or repeated (three or four) daily injections of 30 mumol kg-1 of tetra-THB-spermine were given, and at 4 or 7 days Pu retention was measured in liver, kidneys and femur. Besides tetra-THB-spermine, equimolar doses of tetra-DHB-spermine were injected for comparison, or equimolar doses of diethylene triamine-pentaacetic acid (DTPA) as a reference compound. Histological changes in kidneys and liver were examined after i.p. injections of 30 mumol kg-1 or at 2-13 times higher doses of tetra-THB-spermine. The results show that: (1) Introduction of an additional hydroxy group into the aromatic moieties of tetra-DHB-spermine results in increased hydrophilicity, lower toxicity and a lower renal retention of Pu. (2) Tetra-THB-spermine and tetra-DHB-spermine are similarly effective in removing plutonium from liver and bone. Their efficacies in removing Pu from bone are approximately similar to those of DTPA but for whole-body removal they are generally inferior. (3) Multiple (30 mumol kg-1) of tetra-THB-spermine were no more effective than a single injection at mobilizing Pu from the liver. (4) Four injections of tetra-THB-spermine induced cloudy swelling and fatty degeneration in epithelial cells of the proximal convoluted tubules. At levels of 400 mumol kg-1 tetra-THB-spermine produced severe degenerative glomerular lesions, foci of liver necrosis and thromboses of the portal vein branch.